Molecular Interplay Between PTEN, ARID1A, PD-L1, and MMR in Asian Ovarian Clear Cell Carcinoma: Implications for Immunotherapy Response and Patient Stratification

• Published in: International journal of molecular sciences Vol. 26; no. 10; p. 4915
• Main Authors: Wu, Chen-Hsuan, Lin, Hao, Ou, Yu-Che, Fu, Hung-Chun, Yang, Ming-Yu, Huang, Chao-Cheng
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 20.05.2025; MDPI
• Subjects: Adenocarcinoma, Clear Cell - genetics; Adenocarcinoma, Clear Cell - metabolism; Adenocarcinoma, Clear Cell - pathology; Adenocarcinoma, Clear Cell - therapy; Adult; Aged; Asian People; B7-H1 Antigen - genetics; B7-H1 Antigen - metabolism; Biomarkers; Cancer; Carcinoma; Cell cycle; Chemotherapy; Development and progression; DNA Mismatch Repair; DNA-Binding Proteins - genetics; DNA-Binding Proteins - metabolism; Drug therapy; Female; Humans; Immunotherapy; Immunotherapy - methods; Middle Aged; Mutation; Ovarian cancer; Ovarian Neoplasms - genetics; Ovarian Neoplasms - metabolism; Ovarian Neoplasms - pathology; Ovarian Neoplasms - therapy; Patients; Phosphatases; Protein expression; Proteins; PTEN Phosphohydrolase - genetics; PTEN Phosphohydrolase - metabolism; Response rates; Statistical significance; Survival analysis; Transcription Factors - genetics; Transcription Factors - metabolism; Tumors; California; United States; Massachusetts; Taiwan; PD-L1; PTEN; mismatch repair; ovarian clear cell carcinoma; ARID1A
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms26104915

Ovarian clear cell carcinoma (OCCC) represents a distinct histological subtype with a high prevalence in Asian populations and poor chemotherapy response. This study investigated molecular interactions between phosphatase and tensin homolog (PTEN), AT-rich interactive domain 1A (ARID1A), programmed death-ligand 1 (PD-L1), and mismatch repair (MMR) proteins in Asian patients with OCCC. Immunohistochemical analysis was performed on tissue microarrays from 69 OCCC cases. The expression of PTEN, ARID1A, PD-L1, and four MMR proteins was evaluated alongside clinical data. A high prevalence of PTEN loss (78.3%) and ARID1A deficiency (48.8%), with PD-L1 expression in 26.1% and MMR deficiency in 10.1% of cases, was observed. All PD-L1-positive tumors demonstrated concurrent PTEN loss (p = 0.007). MMR deficiency was significantly associated with ARID1A loss (p = 0.049). PTEN loss correlated with worse progression-free survival (PFS) in early-stage disease (p = 0.039). PTEN and ARID1A alterations represent early pathogenic events in Asian OCCC, with PTEN loss significantly impacting PFS in early-stage disease. The correlation between PTEN loss and PD-L1 expression, alongside ARID1A-MMR deficiency association, provides insights into OCCC’s immunological landscape and therapeutic vulnerabilities.